Clinical presentation ranges from asymptomatic to acute gingivostomatitis characterized by fever, lymphadenopathy and the apperarance of characteristic skin lesions.

The incubation period for herpes virus infection is between 2-20 days [12], but the average time between the contraction of the virus and the appearance of symptoms is about 6 days. Herpetic gingivostomatitis is characterized by a sudden onset of pain, with or without fever, accompanied by other symptoms that are less common and include headache, nausea, malaise, and lymphadenopathy [13] [14].

Gingivostomatitis may be also accompanied by pharyngitis, which can result in symptoms related to pain when swallowing. Secondary bacterial infections may also occur, which can result in the appearance of pus-filled erythematous vesicles, although it is not common. 

The hallmark of this infection is the abrupt appearance of initially erythematous skin, followed by formation of intraoral, perioral or gingival whitish or yellowish vesicles that are usually grouped, or even umbilicated. They are transient, often fragile, and rupture within the first few days. Unilateral presentation is observed in virtually all cases. These lesions spontaneously resolve between 2-4 weeks, with the underlying skin being initially hypo- or hyperpigmented; scarring is rarely observed after the infection is completely resolved. The course of the illness may be prolonged in immunocompromised patients.

• Pain

  Symptoms such as fever, pain at the site of infection, enlarged lymph nodes, etc. may occur, and children may often feel weak and refuse to eat and drink due to pain. [symptoma.com]

  The symptoms are red and swollen gingivae; red mucosa, which soon shows vesicles and ulcers; painful oral cavity; and elevated temperature. [medical-dictionary.thefreedictionary.com]

  While most children with primary gingivostomatitis will be asymptomatic, some will experience considerable pain and discomfort and are at risk of dehydration. [ncbi.nlm.nih.gov]

  For children with fever and pain, acetaminophen or ibuprofen can be given. Although you can get these pain medicines without a doctor’s prescription, it is still recommended that you consult a professional regarding the dosage. [smiles-for-kids.com]

• Fever

  If he has a high fever still, take him now! [mamapedia.com]

  It may also appear if high fever is present, which is why gingivostomatitis is sometimes called "fever blisters". [symptoma.com]

  If any signs or symptoms of dehydration occur such as unusual sleepiness, lethargy or persistent fever, contact the pediatrician. [smiles-for-kids.com]

  Fever Blister, Fever Blisters, Sore, Cold, Sores, Cold, herpes labialis, Fever sore, Cold sores lip, Cold sore (herpetic), Herpes on lip, fever blister, herpes febrilis, Herpes Labialis [Disease/Finding], fever sores, lip herpes, herpes lips, herpes [fpnotebook.com]

• Malaise

  Prodromal symptoms, such as fever, anorexia, irritability, malaise and headache, may occur in advance of disease. [ncbi.nlm.nih.gov]

  Systemic symptoms of fever, malaise, and cervical lymphadenopathy typically occur first, followed by the appearance of vesicles that progress to ulcers. The most common age of occurrence is 6 months to 6 years. [dentalcare.com]

  Non-specific symptoms may include cervical lymphadenopathy, malaise and low grade fever, and can occur in the absence of any discrete clinical lesions. [smile-onnews.com]

  The patient usually suffers from prodromal symptoms of fever, malaise and headaches. However as the ulcers are painful there is often difficulty with eating and drinking leading to dehydration and in severe cases morbidity. [bsdht.org.uk]

• Asymptomatic

  While most children with primary gingivostomatitis will be asymptomatic, some will experience considerable pain and discomfort and are at risk of dehydration. [ncbi.nlm.nih.gov]

  Gingivostomatitis is a self-limiting infection and may even have an asymptomatic course, which makes it a rather benign illness. [symptoma.com]

  Genital herpes may be asymptomatic in many people. The virus can be transmitted even if sores are not visible. People with active outbreaks of genital herpes should avoid sexual activity. [ozarkderm.com]

• Lymphadenopathy

  Although a self-limiting disease, this oral infection can cause significant mouth discomfort, fever, lymphadenopathy, and difficulty with eating and drinking. Symptoms may persist for 2 weeks. [ncbi.nlm.nih.gov]

  Case report A 7-year-old girl was referred to a Consultant Paediatrician at Arrowe Park Hospital with a two week history of fever, lymphadenopathy, oral and peri oral ulceration. A diagnosis of PHGS was made on clinical criteria. [nature.com]

  Clinical presentation ranges from asymptomatic to acute gingivostomatitis characterized by fever, lymphadenopathy and the apperarance of characteristic skin lesions. [symptoma.com]

• Common Cold

  The reactivation triggers include: UVB radiation from sunlight, oral or lip tissue injury, physical or emotional stress, common cold or influenza, fever, and malnutrition. [dentalresource.org]

• Oral Ulcers

  On physical exam, infectious mononucleosis is characterized by oral petechiae with occasional gingivostomatitis and ulceration. [ncbi.nlm.nih.gov]

  Chapter 6 Red and White Lesions 133 Chapter 7 Vesiculobullous Disorders 174 Chapter 8 Oral Ulcerative Diseases 196 Chapter 9 Dermatological Diseases 218 SECTION 4 Diseases of Specific Structures 237 Chapter 10 Temporomandibular Disorders 239 Chapter 11 [books.google.com]

  […] and peri oral ulceration frequently occur. [nature.com]

  Hyperplastic, neoplastic, and related disorders of oral mucosa -- Keratoses and related disorders of oral mucosa -- Oral epithelial tumors, melanocytic naevi, and malignant melanoma -- Infections of the oral mucosa -- Oral ulceration and vesiculobullous [worldcat.org]

  If you find fever and other complicated symptoms arising along with oral ulcers, it is necessary to seek immediate medical treatment. Cure is also important if the oral sores do not show any improvement even after treatment for 2-3 weeks. [primehealthchannel.com]

• Aphthous Stomatitis

  The differential diagnosis of PHG includes acute necrotizing ulcerative gingivitis, herpangina, aphthous stomatitis, candidiasis of the mouth, Steven-Johnson syndrome and hand, foot and mouth disease. [smile-onnews.com]

  It includes but is not limited to trauma, recurrent aphthous stomatitis (commonly known as “canker sores”), syphilis, viral, zoster, erythema multiforme, cyclic neutropenia, acute necrotizing ulcerative gingivitis (Vincent's stomatitis), and oral cancer [journals.lww.com]

  The differential diagnosis of primary herpetic gingivostomatitis has been reviewed in the differential diagnosis of recurrent aphthous stomatitis. [softdental.com]

  RIH may appear similar to traumatic lesions (mechanical/thermal/chemical) or other types of oral mucosal disorders, such as aphthous stomatitis. [jcda.ca]

• Bleeding Gums

  Other symptoms may include: Sores and blisters in the throat, or on the tongue, gums, or lips Swollen, red, or bleeding gums Mouth pain that may make your child irritable and keep him from eating or drinking Drooling Bad breath Swollen glands on the sides [hhma.org]

  Primary herpetic gingivostomatitis can include oral as well as extraoral lesions, swollen and bleeding gums, and symptoms such as pain, fever, irritability, malaise, headache and upper respiratory tract infection. [smile-onnews.com]

  […] and on the back of the mouth Inflammation of gums Bleeding gums Painful sores High fever Bad breath Swollen lymph nodes (particularly around the neck) Watery eyes those are sensitive to light (in severe cases) Discomfort in the mouth Difficulty in eating [momjunction.com]

  Symptoms of gingivostomatitis may include: tender sores on the gums or insides of cheeks (like canker sores, they are grayish or yellow on the outside and red in the center) bad breath fever swollen, bleeding gums swollen lymph nodes drooling, especially [healthline.com]

• Sore Mouth

  Call your provider if: You have mouth sores and fever or other signs of illness Mouth sores get worse or do not respond to treatment within 3 weeks You develop swelling in the mouth Christian JM, Goddard AC, Gillespie MB. [nlm.nih.gov]

  Call your provider if: You have mouth sores and fever or other signs of illness Mouth sores get worse or do not respond to treatment within 3 weeks You develop swelling in the mouth Brice SL. Viral diseases of the skin. [medlineplus.gov]

  Gingivostomatitis is the long name for a condition that results in a very sore mouth. It's caused by a viral infection and is common in children. The symptoms can be mild or severe. [babycenter.com]

  The symptoms can be mild or severe and may include: Not able to chew or swallow Sores on the inside of the cheeks or gums Fever General discomfort, uneasiness, or ill feeling Very sore mouth with no desire to eat Halitosis (bad breath) Herpetic gingivostomatitis [en.wikipedia.org]

• Halitosis

  Sub-mandibular lymphadenitis, halitosis and refusal to drink are usual concomitant findings. [ncbi.nlm.nih.gov]

  […] or gums Fever General discomfort, uneasiness, or ill feeling Very sore mouth with no desire to eat Halitosis (bad breath) Differential Diagnosis Gingivostomatitis symptoms in infants may wrongly be dismissed as teething. [ipfs.io]

  There may be associated fever, cervical lymphadenopathy, halitosis, lethargy, irritability and loss of appetite. [patient.info]

  […] children break adult teeth Service: Gum Disease Treatment A dental hygienist performs initial gum therapy A dental prophylaxis means teeth cleaning Apically repositioned flap periodontal gum surgery Bacteria in the mouth oral infection and germs Bad breath halitosis [nycdentist.com]

• Ulcer

  The ulcerative lesions eventually rupture and become flat, yellow lesions with a red, pseudomembrane ranging from 2 to 5 mm in size. The ulcers are described as painful, quick to bleed, and typically heal without scarring in 2 to 3 weeks. [ncbi.nlm.nih.gov]

  It may disguise other more serious mouth ulcers. [medical-dictionary.thefreedictionary.com]

  Lesions/ulcers for herpetic gingivostomatitis may also be found on the palate and keratinzied gingivae hence aphthous ulcers can be ruled out. [en.wikipedia.org]

  ulcerating, ulceration, ulcerative 707.9 gingivitis 523.10 [icd9data.com]

  Clusters of vesicles or ulcers on an erythematous base are unusual in genital ulcers other than those due to HSV infection. [msdmanuals.com]

• Pruritus

  Genital herpes (herpes genitalis) Pathogen : HSV-2, HSV-1 (less common) Incubation period : 2–7 days Clinical findings Most patients are asymptomatic Genitals: redness, swelling, tingling, pain, pruritus Possibly unusual vaginal discharge Painful lymphadenopathy [amboss.com]

• Tingling

  […] manifestations Dissemination : infection spreads to unusual sites (e.g., lungs, gastrointestinal tract, eyes) Labial herpes (herpes labialis) Pathogen : mostly HSV-1 ( HSV-2 in 10–20% of cases) Clinical features Prodromal symptoms ( ∼ 24 hours ): pain, tingling [amboss.com]

  RECURRENT HERPES LABIALIS: Tingling or itching (prodromal signs) occurs at the infection site before the lip blisters actually appear. Then, clusters of blisters (vesicles) erupt. [dentalresource.org]

  One common symptom is the tingling sensation felt by the person who has a condition of HSV-1. In treating this disease condition, the person is given antibiotics to kill the causative virus. [ehealthwall.com]

  Each outbreak starts with a tingling, burning or painful sensation at the site, followed by a red rash that evolves into tiny blisters that eventually open. [americanskin.org]

  Zinc oxide/glycine combination cream reduces blistering, soreness, itching, tingling, and healing times when compared with placebo. ( Clin Fam Pract 2003;5[3];589.) [journals.lww.com]

• Paresthesia

  Usatine, MD In recurrent herpes labialis, symptoms of tingling, pain, paresthesias, itching, and burning precede the lesions in 60 percent of persons. 5 The lesions then appear as clusters of vesicles on the lip or vermilion border ( Figure 1 ). [aafp.org]

Herpetic Gingivostomatitis is diagnosed primarily through clinical examination [15], since the appearance of lesions, the localization, and the accompanying clinical picture are highly specific for this infection. In addition, the diagnosis can be confirmed through several tests:

• Serology - increased titers of anti-HSV IgM antibodies in primary infection, and increased titers of anti-HSV IgG antibodies in recurrent infections [16] .
• Viral cultures - the Tzanck test comprises tissue sampling from freshly ruptured vesicles and Wright-Giemsa staining of the material reveals multinucleated giant cells [17].
• Biopsy of lesions, direct immunofluorescence and polymerase chain reaction (PCR) testing may serve as alternative diagnostic procedures, but they are used in some other circumstances (eg. PCR techniques are used when suspecting herpes encephalitis).

Serology and viral cultures are the methods of choice for confirming the clinical suspicion of a herpes infection [18]. Additional tests should be performed if these recurrences are frequent, to rule out possible underlying illnesses that predispose the patient to these infections, including HIV testing and malignancy.

This infection is self-limiting and it can resolve without treatment. However, when patients experience symptoms such as pain and high fever, symptomatic therapy may be given to reduce the burden of the disease. When the infection is severe, antiviral therapy may be initiated in order to reduce the duration and severity of symptoms [19]. Acyclovir is an antiviral agent that is used primarily for treatment of herpetic infections and it can be used either topically or systemically. 

Initially, herpetic gingivostomatitis is managed through symptomatic therapy, such as administration of acetaminophen or ibuprofen. Occasionally, local anesthetics such as dyclonine 0.5% liquid or benzocaine ointment are used directly with a swab to reduce pain.

If antiviral therapy is necessary, which is the case in severer infections, acyclovir can be administered locally, as a 5% ointment, six times daily for about 7 days. Penciclovir 1% cream is an alternative treatment and is applied every two hours for 4 days [20]. Oral therapy for herpetic gingivostomatitis includes acyclovir 15mg/kg PO five times a day for children, for seven days. Other antiviral agents that may be used include valacyclovir and famciclovir.

Primary gingivostomatitis is a self-limiting benign disease, which sometimes resolves without any treatment. Typically, it lasts for about 10-14 days, sometimes up to 3 weeks, when lesions spontaneously subside. Symptomatic, and sometimes antiviral therapy is necessary and in some cases, if the lesions are somewhat larger, a secondary bacterial infection may occur, which may require local antibiotic therapy. 

Recurrences of gingivostomatitis may occur and they are usually triggered by certain factors that suppress the activity of the immune system. Like primary infections, they are also self-limiting, but may be debilitating and frustrating for patients if they recur more often.

Gingivostomatitis is one of the many forms of infection caused by the two herpes viruses : HSV-1 and HSV-2, with HSV-1 causing about 80-90% of cases [3] [4]. Herpes simplex virus is a double-stranded DNA virus, which establishes infection by penetrating the mucosal membranes and skin after direct inoculation through contact with infected individuals. Once it reaches the skin, it causes lysis of the cells and development of vesicles that are hallmarks of this disease. After causing the primary infection, herpes virus infects the innervating neurons and travels to the ganglia (most commonly the trigeminal ganglia), where it remains dormant. This is the reason why herpes virus can cause recurring infections, although our immune system, mainly CD8+ T cells, suppresses its replication. 

This infection is most commonly observed among children and young adults, although it can be seen in patients of any age and sex. It is estimated that up to 90% of the population has already contracted the virus by the age of 40 and up to 40% of individuals that harbor the virus have recurrent infections [5] [6].

The virus is transmitted from person-to-person, through close or direct contact with the skin or mucosa of the infected individual. HSV-1 is transmitted through hand and oral contact, mainly through saliva, while HSV-2 is primarily transmitted through sexual contact (responsible for the vast majority of genital herpes infections). A growing incidence of HSV-2 as a cause of oral herpetic infections has been observed, which was not the case in the past [7].

Individuals at risk of contracting the infection are those who are in close contact with people exhibiting an active infection. Gingivostomatitis is a self-limiting infection and may even have an asymptomatic course, which makes it a rather benign illness. However, recurrent infections may occur, most likely due to a compromise of the immune system, which enables the virus to replicate and re-establish infection. Certain factors that may trigger such events include UV radiation, emotional and physical stress [8], menstruation, and long-term immunosuppression such as chemotherapy, infection by human immunodeficiency virus (HIV) [9] [10] [11], or immunosuppressive drugs. It may also appear if high fever is present, which is why gingivostomatitis is sometimes called "fever blisters". 

The virus is shed during active infection and up to three weeks after the infection is resolved, which illustrates that direct and close contact during this time period should be avoided, in order to prevent transmission of the virus.

Once herpes virus is inoculated into the skin, it causes lytic infection of cells at the site of infiltration. Through lysis of cells via degradation of host cell DNA and disruption of the cytoskeleton, it causes tissue injury and avoids the immune response by travelling from cell-to-cell and avoiding the extracellular environment where it can be targeted by the immune system. Once it replicates at the site of initial infection, the virus migrates into the innervating neurons and travels to the sensory nerve ganglia where it remains dormant, most commonly reaching the trigeminal ganglia. The use of neurons as sites of replication and travel are likely the cause of pain that can sometimes be debilitating. 

Although gingivostomatitis is usually a result of primary infection by HSV, reactivation of the virus from sensory ganglia may occur and cause recurrent mucocutaneous infections in the same perioral and oral regions. However, these infections are usually milder in their course and have a shorter duration, due to the existence of immune memory. A more effective immune response is mounted under such circumstances.

Transmission of the virus, as mentioned previously, occurs through close or direct contact with secretions or lesions of an individual with active infection, but transmission may also occur weeks after resolution of the infection. For these reasons, preventive strategies include avoiding contact with these individuals, particularly during the active phases of infection, together with proper hygiene measures. Sharing of glasses, toothbrushes, eating utensils and other materials that may contain saliva of individuals affected by this disease should be avoided.

Herpetic gingivostomatitis is one of the most common clinical manifestations of primary herpes simplex virus infection [1]. Herpes simplex type 1 (HSV-1) is responsible for the majority of infections, while herpes simplex type 2 (HSV-2) is the causative agent in only a small number of cases [2]. This type of infection is most commonly observed in children, but it may occur in any individual. The virus is contracted through close contact with individuals who shed the virus, such as those with active infection. It is not uncommon for the condition to be "asymptomatic", but typical presentation is the appearance of erythematous and grouped vesicles in the oral and perioral area, with or without further symptomatology, such as pain, excessive salivation and fever. Other symptoms, such as lymphadenopathy, malaise and headaches may occur and vesicles often burst and lead to the development of perioral ulcers and crusts. It is a self-limiting disease and can spontaneously resolve, or it can sometimes require symptomatic, even antiviral therapy. However, children may be greatly disturbed, refuse to eat and drink, and sometimes need rehydration therapy. Prevention is achieved through avoiding close contact with individuals who have an active infection. It is important to clarify that herpes virus infection can recur, due to the fact that after the primary infection, the virus remains dormant in nerve ganglia. Gingivostomatitis is one of the most common manifestations of an initial infection by herpes virus.

Herpetic gingivostomatitis is a painful viral infection of the gums and other parts of the mouth caused by the herpes virus. The infection results in reddish skin and tiny vesicles that rupture and turn into crusts, usually occurring on one side of the face. Infection most commonly occurs in children, and when it does, it is most commonly a "primary infection", meaning that it is the first time they are encountering the herpes virus. From then on, recurrent infections may occur, as the virus "sleeps" in neurons of the face after the initial infection. Symptoms such as fever, pain at the site of infection, enlarged lymph nodes, etc. may occur, and children may often feel weak and refuse to eat and drink due to pain. The physician should recognize the typical appearance of the skin lesions and immediately suspect this infection, but a definite diagnosis is achieved through swabs from the affected skin and further testing. This infection can last up to a few weeks, after which it resolves, usually without any signs of scarring on the skin. Recurrences may occur later in life. Treatment may be necessary if the infection does not resolve on its own and includes application of local anesthetics, or sometimes antiviral agents on the affected skin. In rare cases, oral intake of antiviral agents, such as acyclovir, may be necessary to treat this infection. 

1. McCullough MJ, Savage NW. Oral viral infections and the therapeutic use of antiviral agents in dentistry. Aust Dent J. 2005;Dec;50(Vol.2):S31-5.
2. Wolff K, Johnson, RA, Suurmond D, Fitzpatrick TB. Fitzpatrick's color atlas and synopsis of clinical dermatology. 2005;New York:McGraw-Hill. . Medical Pub. Division.
3. Soames J V, Southam J C. Oral pathology; Oxford University Press. 1998;p183–186.
4. Nieuwenhuis R F, van Doornum G J, Mulder P G et al. Importance of herpes simplex virus type-1 in primary genital herpes. Acta Derm Venereol 2006;86:129–134.
5. Embil JA, Stephens RG, Manuel FR. Prevalence of recurrent herpes labialis and aphthous ulcers among young adults on six continents. Can Med Assoc J. 1975;Oct 4;113(7):627-30.
6. Langlais RP, Miller CS. Color Atlas of Common Oral Diseases. Williams & Wilkins. 1992;84, 118.
7. Sapp JP, Eversole LR, Wysocki GP. Contemporary Oral and Maxillofacial Pathology. Mosby. 2004;p200-201.
8. Stock C, Guillan-Grima F, Hermosa de Mendoza J et al. Risk factor of herpes simplex type I (HSV-1) infection and lifestyle factors associated with HSV-1 manifestations. Eur J Epidemiol 2001;17:885–890.
9. Liang GS, Daikos GL, Serfling U, Zhu WY, Pecoraro M, Leonardi CL, Fischl MA, Penneys NS. An evaluation of oral ulcers in patients with AIDS and AIDS-related complex. J Am Acad Dermatol. 1993;Oct;29(4):563-8.
10. Itin PH, Lautenschlager S. Viral lesions of the mouth in HIV-infected patients. Dermatology. 1997;194(1):1-7.
11. Krone MR, Wald A, Tabet SR, Paradise M, Corey L, Celum CL. Herpes simplex virus type 2 shedding in human immunodeficiency virus-negative men who have sex with men: frequency, patterns, and risk factors. Clin Infect Dis. 2000;Feb;30(2):261-7.
12. Faden H. Management of primary herpetic gingivostomatitis in young children. Pediatr Emerg Care. 2006;Apr;22(4):268-9.
13. Kolokotronis A, Doumas S. Herpes simplex virus infection, with particular
    reference to the progression and complications of primary herpetic
    gingivostomatitis. Clin Microbiol Infect. 2006;Mar;12(3):202-11.
14. Arduino P G, Porter S R. Oral and perioral herpes simplex virus type 1 (HSV-1) infection: review of its management. Oral Dis 2006;12:254–270.
15. Amir J, Straussberg R, Harel L et al. Evaluation of a rapid enzyme immunoassay for the detection of herpes simplex antigen in children with herpetic gingivostomatitis. Pediatr Infect Dis J 1996;15:627–629.
16. Siegel MA. Diagnosis and management of recurrent herpes simplex infections. J Am Dent Assoc. 2002. Sep;133(9):1245-9.
17. CM Lee, DD Damm, BW Neville, C Allen, Bouquot J Oral and Maxillofacial Pathology, 3rd ed. St Louis: Elsevier-Saunders. 2009;St Louis:Elsevier.
18. MS Greenberg. Ulcerative vesicular and bullous lesions. In: Greeberg MS, Glick M, (Editors). Burket’s Oral Medicine, Diagnosis and Treatment, 10th ed. 2003;BC Decker Inc.; USA. p68–71.
19. Van de Perre P et al. Herpes simplex virus: a new era? Lancet. 2012;Vol. 379(9816):598-599.
20. Amir J, Harel L, Smetana Z, Varsano I. Treatment of herpes simplex gingivostomatitis with aciclovir in children: a randomised double blind placebo controlled study. BMJ. 1997;314(7097):1800–1803.